Penicillin S-oxide ring

Azodiisobutyronitrile Penicillin S-oxide ring by radical rearrangement... 

Participation s. Neighboring group participation Pathway control -, reaction of oximes with nitrosyl chloride 26, 258s31 Pearson degradation 9,294 Penicillin S-oxide ring... 

An interesting reaction related to the ring expansions of penicillin S-oxides (208) was observed in the thermal rearrangement of 2,2,4A-tetramethyl-thiethan-3-one 1-oxide to the five-membered thiolane ring 209. Oxidation attempts of these thermally unstable thietanone oxides led via ring opening to the more stable heterocycle. The reaction mechanism (Scheme 11) was... 

Penicillin-S-oxide liefern bci der Behandlung mit Trimethylphosphit unter Offnung beider Ringe und Recyclisierung N-substituierte 2-Alkoxy-4-(l-diphenylmethoxycarbonyl-2-me-thyl-2-propcnylaminocarbonyl)-l, 3-thiazole (80%)909 ... 

Immobilized cells of S. clavuligerus NP1, entrapped on a polymeric matrix, were able to perform oxidative ring expansion of penicillin G into DAOG. Cells entrapped in polyethyleneimine barium alginate (1.5%) were able to sustain activity for at least four 2-hr cycles, whereas free resting cells were inactive after the second cycle. 

Finally, there are a mixed bag of oxidases, catalysing ethylene formation in plants and many other diverse reactions, illustrated in Figure 13.20, by isopenicillin N-synthase, IPNS, which catalyses the cyclisation of the heterocyclic P-lactam ring. The importance of penicillin- and cephalosporin-related antibiotics in clinical medicine cannot be underestimated and has stimulated the study of their biosynthetic pathways. A key step in the biosynthesis of these antibiotics involves oxidative ring closure reactions of S-(L-a-aminoadipoyl)-L-cysteinyl-D-valine (ACV) to form isopenicillin N, the precursor of penicillins and cephalosporins, catalysed by IPNS (Figure 13.20). The overall reaction utilizes the full oxidative potential of O2, reducing it to two molecules of H2O. As discussed earlier, these enzymes are technically oxidases and the four electrons required for dioxygen reduction come from the substrate. 

Oxidation reactions on the sulfur atom of penicillins remain the most important reactivity of S-1 encountered in the literature. Penam sulfoxides and sulfones are indeed important compounds as they confer to the skeleton an ease of thiazolidine ring opening by weakening the C(5)-S(l) and S(l)-C(2) bonds (see Section 2.03.5.9) <2004CHE816>. In particular, the former constitute key intermediates in ring-expansion transformations from penams to cephems (see Section 2.03.5.9), while the latter have a special biological interest as /3-lactamase inhibitors (e.g., sulbactam, tazobactam see Sections 2.03.1, 2.03.5.2, and 2.03.12.4). Since CHEC-II(1996) covers all the aspects of these oxidation reactions on the S-1 atom of penicillins, this section focuses on the most relevant recent papers. As there is no particular change in the subject, only a few articles have been released since 1995. 

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